title: Early host cell targets of Yersinia pestis during primary pneumonic plague.
abstract: Inhalation of Yersinia pestis causes primary pneumonic plague, a highly lethal syndrome with mortality rates approaching 100%. Pneumonic plague progression is biphasic, with an initial pre-inflammatory phase facilitating bacterial growth in the absence of host inflammation, followed by a pro-inflammatory phase marked by extensive neutrophil influx, an inflammatory cytokine storm, and severe tissue destruction. Using a FRET-based probe to quantitate injection of effector proteins by the Y. pestis type III secretion system, we show that these bacteria target alveolar macrophages early during infection of mice, followed by a switch in host cell preference to neutrophils. We also demonstrate that neutrophil influx is unable to limit bacterial growth in the lung and is ultimately responsible for the severe inflammation during the lethal pro-inflammatory phase.
authors.affiliation: Department of Microbiology and Immunology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States of America.
authors.forename: Roger D
authors.initials: RD
authors.lastname: Pechous
authors.forename: Vijay
authors.initials: V
authors.lastname: Sivaraman
authors.forename: Paul A
authors.initials: PA
authors.lastname: Price
authors.forename: Nikolas M
authors.initials: NM
authors.lastname: Stasulli
authors.forename: William E
authors.initials: WE
authors.lastname: Goldman
mesh_terms: D000818:Animals; D005260:Female; D007249:Inflammation / Q000276:immunology / Q000473:pathology; D051379:Mice; D020556:Neutrophil Infiltration / Q000276:immunology*; D009504:Neutrophils / Q000276:immunology* / Q000473:pathology; D010930:Plague / Q000276:immunology* / Q000473:pathology; D018410:Pneumonia, Bacterial / Q000276:immunology* / Q000382:microbiology / Q000473:pathology; D015010:Yersinia pestis / Q000276:immunology*